Impact of MRI markers in subcortical vascular dementia: a multi-modal analysis in CADASIL.
CADASIL is an arteriopathy caused by mutations of the Notch3 gene. White matter hyperintensities (WMH), lacunar lesions (LL), cerebral microhemorrhages (CM), brain atrophy and tissue microstructural changes are detected on MRI. Using an integrated multi-modal approach, we examined the relative impact of lesion burden and location of these MRI markers on cognitive impairment and disability. Multi-modal imaging was performed on 147 patients from a two-center cohort study. Volume of LL, WMH and number of CM was determined. Whole brain mean apparent diffusion coefficient (mean-ADC) and brain parenchymal fraction (BPF) were measured. In multivariate models accounting for lesion burden and location, volume of LL, mean-ADC, and BPF each had an independent influence on global cognitive function and disability. BPF explained the largest portion of the variation in cognitive and disability scores (35-38%). Brain atrophy has the strongest independent influence on clinical impairment in CADASIL when all MRI markers in the disease are considered together. The results suggest that the clinical impact of cerebral tissue loss plays a principal role in this genetic model of subcortical ischemic vascular dementia.
Viswanathan
Anand
A
Department of Neurology, CHU Lariboisière, Assistance Publique des Hôpitaux de Paris, Paris, France.
Godin
Ophelia
O
Jouvent
Eric
E
O'Sullivan
Michael
M
Gschwendtner
Andreas
A
Peters
Nils
N
Duering
Marco
M
Guichard
Jean-Pierre
JP
Holtmannspötter
Markus
M
Dufouil
Carole
C
Pachai
Chahin
C
Bousser
Marie-Germaine
MG
Dichgans
Martin
M
Chabriat
Hugues
H
D001921:Brain / Q000473:pathology*; D046589:CADASIL / Q000473:pathology*; D005260:Female; D005602:France; D005858:Germany; D006801:Humans; D007089:Image Enhancement / Q000379:methods; D007090:Image Interpretation, Computer-Assisted / Q000379:methods*; D008279:Magnetic Resonance Imaging / Q000379:methods*; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity